Gene Delivery of Cytochrome P450 Epoxygenase Ameliorates Monocrotaline-induced Pulmonary Artery Hypertension in Rats

Overview

Journal Am J Respir Cell Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2010 Feb 2

PMID 20118222

Citations 15

Authors

Changlong Zheng

Luyun Wang

Rui Li

Ben Ma

Ling Tu

Xizhen Xu

Ryan T Dackor

Darryl C Zeldin

Dao Wen Wang

Affiliations

Soon will be listed here.

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening disease that leads to progressive pulmonary hypertension, right heart failure, and death. Endothelial dysfunction and inflammation were implicated in the pathogenesis of PAH. Epoxyeicosatrienoic acids (EETs), products of the cytochrome P450 epoxygenase metabolism of arachidonic acid, are potent vasodilators that possess anti-inflammatory and other protective properties in endothelial cells. We investigated whether gene delivery with the human cytochrome P450 epoxygenase 2J2 (CYP2J2) ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. Significant pulmonary hypertension developed 3 weeks after the administration of MCT, but gene therapy with CYP2J2 significantly attenuated the development of pulmonary hypertension and pulmonary vascular remodeling, without causing changes in systemic arterial pressure or heart rate. These effects were associated with increased pulmonary endothelial NO synthase (eNOS) expression and its activity, inhibition of inflammation in the lungs, and transforming growth factor (TGF)-β/type II bone morphogenetic protein receptor (BMPRII)-drosophila mothers against decapentaplegic proteins (Smads) signaling. Collectively, these data suggest that gene therapy with CYP2J2 may have potential as a novel therapeutic approach to this progressive and oftentimes lethal disorder.

Citing Articles

CYP2J2 and EETs protect against pulmonary arterial hypertension with lung ischemia-reperfusion injury in vivo and in vitro.

Ding Y, Tu P, Chen Y, Huang Y, Pan X, Chen W Respir Res. 2021; 22(1):291.

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Dihydroxyeicosatrienoic Acid, a Metabolite of Epoxyeicosatrienoic Acids Upregulates Endothelial Nitric Oxide Synthase Expression Through Transcription: Mechanism of Vascular Endothelial Function Protection.

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Vascular Lipidomic Profiling of Potential Endogenous Fatty Acid PPAR Ligands Reveals the Coronary Artery as Major Producer of CYP450-Derived Epoxy Fatty Acids.

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